Project Summary/Abstract: This F31 award will allow PhD candidate Natalie Keirns training and research experiences that will advance her toward her goal of ultimately becoming an independent investigator of social and biological risk/protection factors in obesity and cardiometabolic disease. Weight-based stigma is a pervasive experience for individuals with overweight/obesity (OW/OB) and is a phenomenon that may be involved in the development of health consequences affiliated with obesity (e.g., cardiovascular disease, CVD). Elevated cortisol, and chronic stress system activation more generally, has been repeatedly linked to numerous negative health outcomes, including increased inflammation, risk for cardiac events, and mortality. Of note, these are the very same outcomes commonly linked to OW/OB. A scientific understanding of stigma suggests that stigma itself may play a causal role in these outcomes. Current conceptual models purport that weight stigma acts as a chronic stressor, leading to increased levels of cortisol, with cortisol then contributing to weight gain and, as a result, increased stigma. Further, other and more extensively studied stigmas (e.g., racism) are also considered chronic stressors, and they have been linked to comparable detriments to health. As these health consequences are among the most prevalent adverse outcomes of obesity, it is imperative to further understand how weight stigma may play a role in the development of these weight-related health consequences. The proposed study aims to further elucidate the biological mechanisms by which weight stigma has adverse health effects, particularly via inflammatory pathways. Using a between-subjects experimental stress reactivity design, participants will undergo a weight stigma or control stress manipulation. Pre- and post-task blood draws will measure the primary outcome: changes in inflammatory markers (i.e., IL-6, IL-1?). Measurements at pre-task and 30, 60, and 90-min post-task will observe the acute effects of experiencing weight stigma on inflammation. The project will also investigate internalization of weight stigma as a potential moderator of the stigma-health relationship. Supported by previous research on a) the role of chronically elevated cortisol in the body and b) related stigma-based chronic stressors, our central hypothesis is that weight stigma stress will lead to increased acute immune reactivity as measured by the inflammatory response. This novel study will contribute critical knowledge urgently needed by the scientific and public health community to understand how weight stigma may contribute to the development of or exacerbate weight-related disease through activation of the immune system. Further, this project will serve as an incredibly valuable training experience for a promising young scholar by providing the opportunity to learn about weight stigma and sophisticated biomarker assessment techniques from leading experts in the field and by promoting interdisciplinary collaboration.